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Substituted amfetamine
Substituted amfetamines come in three major flavours, the stimulant-type, such as metamfetamine and amfetamine, the empathogens-entactogens (EEs, that is, those with properties similar to MDMA ecstasy) and psychedelic amfetamines (PAs). The stimulant-type amfetamines are generally at their most potent in their S-form, whereas in the case of EEs the R-isomers are generally more potent, the same holds for PAs. They are are all known to cause lasting damage to dopaminergic and serotonergic neurons in laboratory animals, although in humans, this is not completely clear,As unlike laboratory animals we generally do not kill humans after they abuse drugs so we can perform the detailed examination of their brains that can only be done at autopsy for some of the most notoriously-abused ones (like metamfetamine and ) clear cognitive deficits and an increased risk of neurodegenerative disorders in the future have been demonstrated from observational studies. As for amfetamines at therapeutic doses like dexamfetamine and mixed amfetamine salts (Adderall) at their respective (significantly lower) doses it is less clear as to their long-term impact on neurological functions like cognition. The mechanism behind this destruction of dopaminergic and serotonergic neurons is not 100% clear, but it is believed to involve reactive oxygen species (ROS), that is, free radicals that react with pretty much any organic molecule they meet, including those in the proteins and strands of neurons.Heal, DJ; Smith, SL; Gosden, J; Nutt, DJ (June 2013). "Amphetamine, past and present--a pharmacological and clinical perspective.". Journal of Psychopharmacology 27 (6): 479–96. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642.Ares-Santos, S; Granado, N; Moratalla, R (May 2013). "The role of dopamine receptors in the neurotoxicity of methamphetamine.". Journal of Internal Medicine 273 (5): 437–53. doi:10.1111/joim.12049. PMID 23600399. ROS from amfetamines are believed to be produced via the breakdown of dopamine and serotonin via monoamine oxidase. More indirect mechanisms such as dopamine-mediated neurotoxicity via actions on the dopamine receptors are also possible. Consequently, it is theoretically possible that a high amount of antioxidants or monoamine oxidase inhibitors (MAOIs; found in plants of the Passiflora and Harmala (illegal in Australia) genus are good examples) in one’s diet may protect one’s neurons from this ill effect, although this is yet to be demonstrated in human clinical trials. I should mention, however, that combining with an amfetamine, especially MDMA is associated with a significantly increased risk of ill effects such as the serotonin syndrome, which can be a fatal condition.Perfeito, R; Cunha-Oliveira, T; Rego, AC (September 2013). "Reprint of: revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease-resemblance to the effect of amphetamine drugs of abuse.". Free Radical Biology & Medicine 62: 186–201. doi:10.1016/j.freeradbiomed.2013.05.042. PMID 23743292.Thrash, B; Thiruchelvan, K; Ahuja, M; Suppiramaniam, V; Dhanasekaran, M (November-December 2009). "Methamphetamine-induced neurotoxicity: the road to Parkinson's disease." (PDF). Pharmacological Reports 61 (6): 966–77. PMID 20081231.Yamamoto, BK; Moszczynska, A; Gudelsky, GA (February 2010). "Amphetamine toxicities: classical and emerging mechanisms.". Annals of the New York Academy of Sciences 1187: 101–21. doi:10.1111/j.1749-6632.2009.05141.x. PMC 3955986. PMID 20201848. Notes Reference list Category:Drugs of abuse Category:Substituted phenethylamines